Abstract

Background: Ischemic stroke is one of causes of atherosclerotic diseases, and is closely associated with vulnerable plaque at the origin of the internal carotid artery. Several studies have shown that neovascularization in atheromatous plaque serves as a reliable maker of plaque vulnerability.Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of carotid intraplaque neovascularization. The aim of the present study was to investigate the histopathologic findings of enhanced carotid plaque on CEUS. Methods: We studied consecutive 18 patients (16 men, mean age 69.4 ± 6.7 years) who underwent carotid endarterectomy. Enhanced plaque was classified into two subgroups: a spotty pattern as moving bright spots within plaque ( Figure 1 A, Panel A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque ( Figure 1 B, Panel A). Sonazoid (Daiich-Sankyo, Tokyo, Japan), perflurobutane microbubbles, was used as the contrast agent. A bolus intravenous injection of Sonazoid (0.015 mL/kg body weight (0.12 μ L perflurobutane microbubble /kg body weight)) was performed via the peripheral venous line followed by a flush with 10 mL of normal saline. We investigated the association between enhanced plaque on CEUS and histopathologic findings. Results: CEUS revealed enhanced plaque in 11 (61.1%) of 18 patients. Only a spotty pattern (spotty subgroup) was observed in 5 patients, whereas both a spotty and linear pattern (linear subgroup) was observed in 6. The amount of neovascularization was larger in enhanced than in non-enhanced plaque (6.79 ± 5.17/2.5 mm 2 vs. 1.12 ± 0.90/2.5 mm 2 , P=0.001). Furthermore, the enhanced group had more macrophage aggregation (7.76 ± 3.70% vs. 4.23 ± 1.63%, P=0.030) and intraplaque hemorrhage (18.84 ± 14.88% vs. 5.52 ± 9.68%, P=0.013) compared with the non-enhanced group. Thin fibrous cap (<200 μ m) was more frequent in enhanced than non-enhanced plaque (100% vs. 28.6%, P=0.002). All of the enhanced plaques with a linear pattern had fibrous cap rupture, but this was observed in only 20% of those with a spotty pattern (P=0.015, Figure 1 B, Panel B). Conclusions: Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque.

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